Telemedicine and orthopaedic care. A review of 2 years of experience.

The objective of this study was to study the delivery of orthopaedic care via a telemedicine network. This study is a descriptive analysis of orthopaedic teleconsultations done during a 2-year period by three orthopaedic surgeons. Four hundred ten teleconsultations were done during the study period from February 1, 1995, to December 31, 1996. Orthopaedic surgeons engaged in 91 teleconsultations (22% of all teleconsultations). Reasons for orthopaedic teleconsultations were: evaluation and treatment of fracture care (39 cases; 43%); evaluation and treatment of ligamentous injury, joint swelling and infection (32 cases; 35%); postoperative evaluation (16 cases; 18%); and evaluation and treatment of dislocations (four cases; 4%). Sixty-two (68%) of the patients remained in the rural community. Twenty-one (23%) of the orthopaedic teleconsultations were classified as emergent (done immediately). Thirty-five (38%) were urgent (done within 1 to 2 hours of provider request), and 35 (38%) were scheduled. The mean duration of time for teleconsultations was 12.8 minutes. Eighty-seven (96%) of the teleconsultations occurred Monday through Friday. Outcome data were collected on all patients involved in teleconsultations. No adverse patient outcomes occurred. This study suggests telemedicine may be an avenue for the delivery of orthopaedic care to patients residing in areas where orthopaedic specialists are not available.

Decreases in behavioral and striatal neuronal responses to dexamphetamine with aging.

Striatal neurons of mature rats responded to 2.5 mg/kg dexamphetamine with increased multiple unit activity that followed the time course of drug-increased behavior. In contrast, in older (middle-aged) rats striatal neurons failed to respond to dexamphetamine with excitation. Behavioral responses were reduced by half as compared to mature rats. Retesting of these middle-aged rats with dexamphetamine did not result in either improved behavioral or neuronal responses and decreases in spontaneous MUA suggested dexamphetamine neurotoxicity in older animals. Since striatal neuronal responses and behavioral responses to dexamphetamine are greatly reduced, age-related impairment of dopaminergic neurotransmission may lead to in reductions in striatal neuronal excitation as well as feedback from dexamphetamine-induced behavior.

Pharmacological activity profiles of dopamine D-1 and D-2 reception agonists and antagonists on striatal neuronal activity and the response to dexamphetamine in freely moving rats.

1. The effects of dopamine D-1 and D-2 receptor agonists and antagonists were investigated by recording extracellular striatal action potentials in freely moving rats. Dopamine receptor antagonist effects were also evaluated on dexamphetamine-induced excitation of striatal neurons. 2. Striatal neurons responded to SKF 38393, a D-1 agonist, with dose-dependent reductions in activity. At a 2.0 mg/kg dose neuronal activity decreased to 50% of control values. 3. The D-1 antagonist, SCH 23390, at a dose of 4.0 mg/kg decreased striatal neuronal activity by more than 50% and also effectively blocked the effects of 2.5 mg/kg dexamphetamine. 4. LY 171555, a D-2 agonist, at 1.0 or 2.5 mg/kg, did not significantly increase striatal neuronal activity. Although behavioral activation was noted, the neuronal response at the high dose was biphasic with inhibition predominant. 5. The D-2 antagonists haloperidol and sulpiride decreased striatal neuronal activity in a dose-dependent manner and also effectively antagonized the effects of dexamphetamine. The D-2 antagonist, RO 22-1319, at a dose of 2.0 mg/kg completely antagonized increases in striatal neuronal activity after dexamphetamine. 6. These findings suggest that dexamphetamine-induced increases in striatal neuronal activity are due to either stimulation of both D-1 and D-2 receptors, or alternatively, a third dopamine receptor subtype sensitive to both D-1 and D-2 antagonists but not agonists. Furthermore, the concept of specific D-1 and D-2 receptor agonists may require revision as neither SKF 38393 or LY 171555 increased striatal neuronal activity.

Excitation of striatal neurons by dexamphetamine is not abolished by either chloral hydrate or urethane anaesthesia.

In order to understand differences between studies maintaining that dopamine actions are significantly reduced as a result of chloral hydrate anaesthesia or not affected to any appreciable extent, striatal neuronal responses to the indirect dopamine agonist, dexamphetamine, were examined in rats anaesthetized with either chloral hydrate (400 mg/kg) or urethane (1.5 g/kg). Striatal neuronal activity was markedly depressed by chloral hydrate and urethane. However, striatal neurons still responded to 2.5 mg/kg dexamphetamine with marked excitation. These results indirectly support earlier iontophoretic studies on the excitatory action of dopamine on striatal neurons in chloral hydrate-anaesthetized animals. Furthermore, the ability of dexamphetamine, primarily an indirect dopamine agonist, to excite striatal neurons in these anaesthetized animals suggests that stimulation of both D1 and D2 receptors is not abolished by anaesthesia.

The effects of cortical ablation on multiple unit activity in the striatum following dexamphetamine.

Bilateral removal of the fronto-parietal cortex of the rat resulted in decreased spontaneous multiple-unit activity recorded in the striatum of freely-moving rats. Cortical ablations changed the neuronal response in the striatum to systemic administration of dexamphetamine (2.5 mg/kg i.p.) from excitation in control animals (88%) to inhibition in ablated animals (61%). Furthermore, catalepsy, induced by haloperidol, but not by morphine, was markedly attenuated after cortical ablation. These changes were accompanied by a 23% decrease in the specific binding of [3H]spiperone in the striatum. The binding of [3H]met-enkephalin was unaffected by the cortical lesions. Levels of glutamate in the striatum decreased from 8.88 +/- 0.5 mumols/g in control animals to 6.93 +/- 0.37 mumols/g after bilateral cortical ablation. On the other hand, cortical ablations did not alter the content of either the gamma-aminobutyric acid or glutamine of the striatum. It is concluded that the excitatory response, observed in striatal neurons in freely-moving animals, is dependent upon an intact cerebral cortex and requires intact cortico-striatal afferents. The results further suggest that neurons in the striatum are under the tonic influence of glutamate, released from cortico-striatal afferents. Lastly, some dopamine D2 binding sites in the striatum are located on cortico-striatal afferent terminals and blockade of these striatal D2 sites may be involved in the induction of catalepsy by neuroleptic drugs.

Activation of striatal neurons by dexamphetamine is antagonized by degeneration of striatal dopaminergic terminals.

Unilateral degeneration of nigrostriatal dopaminergic terminals by the intranigral infusion of 6-OHDA produced a decrease in spontaneous multiple unit activity (MUA) in both the ipsilateral and contralateral striata of freely moving rats. Nigral lesions also attenuated the dexamphetamine-induced increase in MUA in the ipsilateral but not in the contralateral striatum. The magnitude of the attenuation in the ipsilateral striatum was directly proportional to the percent depletion of dopamine. Similarly degeneration of dopaminergic terminals produced by a unilateral application of 6-OHDA into the striatum lowered spontaneous MUA and completely antagonized the dexamphetamine-induced increase in MUA in the dopamine-depleted striatum. Although the spontaneous MUA in striata contralateral to a local 6-OHDA treatment was significantly reduced, the response to dexamphetamine was normal. Both striatal and nigral application of 6-OHDA produced dopamine depletion in the ipsilateral striatum and an increase in striatal dopamine levels on the contralateral side. Striatal application of 6-OHDA did not alter dopamine levels in either the olfactory tubercles, piriform cortex or cingulate cortex. It is concluded that the increase in MUA observed in the striatum following dexamphetamine treatment is critically dependent upon the release of dopamine in the striatum. These results support the concept that dopamine may have an excitatory action on some striatal neurons.

Reduction of the rewarding effect of brain stimulation by a blockade of dopamine D1 receptor with SCH 23390.

The subtype of dopamine receptor related to the rewarding effect of brain stimulation was determined in 17 rats. The animals were trained to contact a dry spout to receive stimulation through electrodes implanted into the lateral hypothalamic area, ventral tegmental area, or dorsal raphe nucleus. The dopamine D1 blocking agent SCH 23390, 0.08 mg/kg IP, completely suppressed responding. The D2 receptor blocker sulpiride, 50 mg/kg IP, or the serotonin receptor blocker metergoline, 5 mg/kg IP, did not suppress responding. The ED50 for SCH 23390 was 0.022 mg/kg IP. In a runway, rats were trained to run for rewarding goal stimulation consisting of a train of pulses delivered to the lateral hypothalamus. After injection of SCH 23390, 0.01 mg/kg IP, animals showed significantly slower running speed, but their speed returned to normal if the number of pulses in the goal stimulation was increased 2.6 times. These results indicate that blockade of D1 receptors, but not D2 receptors, reduces the rewarding effect of brain stimulation.

Immobilization of rats modifies the response of striatal neurons to dexamphetamine.

The effect of dexamphetamine (DEX) on striatal multi-unit activity was examined in freely moving rats and again 24 or 48 hr later during immobilization. Animals which in the freely moving state responded with striatal activation following DEX, 1 mg/kg IP, did not respond to this dose of DEX after immobilization. Similarly with DEX 2.5 mg/kg IP, the incidence of excitatory responses seen in freely moving animals decreased to 18% after immobilization, and the incidence of inhibition and biphasic responses increased from 0% in freely moving animals to 52% in immobilized preparations. The results suggest that the response of striatal neurons to DEX is dependent upon the behavioural state of the animal. Furthermore, these findings indicate that the central actions of DEX are more complex than previously believed, and raises the speculation that the excitatory effects of DEX on striatal neurons may be mediated through excitatory striatal afferents.

Responses of striatal neurons to anesthetics and analgesics in freely moving rats.

The effects of anaesthetics and analgesics on striatal neurons were examined in freely moving rats by recording extracellular action potentials of neurons in the striatum. Spontaneous multiple unit activity was reduced to less than 20% of control firing rates following either pentobarbital 35 mg/kg i.p., halothane 3%, chloral hydrate 400 mg/kg i.p., or urethane 1.5 g/kg i.p. Morphine 15 mg/kg i.p., decreased striatal neuronal firing whereas ketamine, 50 mg/kg i.p., excited striatal neurons. The only analgesic agent tested that did not significantly affect striatal neuronal firing was nitrous oxide (70% N2O/30% O2). These findings demonstrate that nitrous oxide is a suitable analgesic which can be used to alleviate stress and pain associated with immobilization procedures without appreciably altering spontaneous striatal discharge rates.

The role of afferents from the parafascicular-centromedian complex in the excitatory striatal neuronal response to dexamphetamine in freely moving animals.

The striatal neuronal response to dexamphetamine, 2.5 mg/kg, was studied in normal freely moving animals and in freely moving animals with unilateral lesions of the parafascicular-centromedian complex. Whereas dexamphetamine produced predominantly excitation of striatal neurons in control animals, the predominant response in lesioned animals was inhibition. In lesioned animals dexamphetamine-induced behavioral activation was unchanged. It is concluded that the PF-CM complex plays an important role in the striatal neuronal response to dexamphetamine in freely moving animals and may be one of the neural substrates conveying sensory feedback from drug-induced behavior to the striatum.

Bilateral ablation of the corticostriatal projection: behavioral, biochemical and electrophysiological correlates.

Striatal neuronal responses to dexamphetamine, 2.5 mg/kg i.p., were examined in normal and bilateral cortically ablated freely moving rats using multiunit recording. Striatal glutamate levels, D1 and D2 receptor binding, and haloperidal catalepsy were examined in both sham-operated and ablated animals. Bilateral ablation of the cortex, while not affecting dexamphetamine-induced behavioral activation, changed the striatal neuronal response from predominantly excitation to inhibition. Striatal glutamate levels were reduced 22% in ablated animals; and dopamine D-2 receptor binding sites were similarly decreased by 20%. In bilaterally ablated animals, haloperidol-induced catalepsy was greatly reduced.

Immobilization-induced changes in the response of striatal neurons to dexamphetamine.

Bipolar multiple unit recording electrodes were implanted in the striata of male Long-Evans rats 5-7 days prior to experimentation. In subsequent experiments, striatal neuronal activity in response to dexamphetamine (1.0 or 2.5 mg/kg i.p.) was recorded in either freely moving or immobilized, artificially-respired rats. Whereas dexamphetamine produced only excitation of striatal neurons in freely moving animals, a multiplicity of responses, ranging from excitation to inhibition, and including biphasic as well as no change responses were observed in immobilized animals. It is concluded that the absence of dexamphetamine-induced behavior in immobilized animals modifies the striatal neuronal response to dexamphetamine, possibly through alteration of the activity of excitatory striatal afferents.

Dissociation of the antiaggression and serotonin-depleting effects of fenfluramine.

Fenfluramine or norfenfluramine produced a marked and persistent depletion of whole-brain serotonin and antagonized potently the apomorphine-induced aggression response in Long Evans male rats. Chronic treatment with fenfluramine or norfenfluramine resulted in the development of complete tolerance to the antiaggression action of fenfluramine whereas tolerance to the serotonin-depleting action was not observed. Pretreatment with chlorimipramine antagonized both the antiaggression and the serotonin-depleting activity of fenfluramine yet the antiaggression activity of haloperidol was unaffected. Neither p-chlorophenylalanine nor the combination of alpha-methyl-p-tyrosine and reserpine affected the antiaggression activity of fenfluramine. It is concluded that the serotonin-depleting and antiaggression effects are dependent upon the ability of fenfluramine to gain access into the serotonergic neuron and that whereas serotonin release can account for the antiaggression action, release does not seem to explain adequately the depleting action of fenfluramine.

2-(Alkoxyaryl)-2-imidazoline monoamine oxidase inhibitors with antidepressant activity.

Unlike the related noncyclic amidines which are broad-spectrum cestocides, a number of 2-imidazolines substituted in the 2 position by alkoxyaryl groups were not highly active in screening tests against the mouse tapeworms Hymenolepsis nana and Oochoristica symmetrica. Certain of the 2-(4-alkoxynaphthyl)-2-imidazolines and 2-(6-alkoxy-2-naphthyl)-2-imidzolines, however, had activity interpreted as antidepressant in the mouse. This activity paralleled in vitro irreversible inhibitory activity against mouse brain MAO for those where no substitution is present on the imidazoline ring. This irreversibility probably has a different origin from that postulated to explain the irreversible MAO inhibition of proparglic, cyclopropyl, and other "chemically reactive" MAO inhibitors.

Synthesis and dopaminergic activity of (+/-)-, (+)-, and (-)-2-dipropylamino-5-hydroxy-1,2,3,4-tetrahydronaphthalene.

In an effort to identify further the structural requirements for central dopamine receptor agonists, some monohydroxyl analogs of the known agonist 5,6-dihydroxy-2-dipropylamino-1,2,3,4-tetrahydronaphthalene were synthesized. They were examined for production of emesis in dogs and stereotyped behavior in rats. The most potent was 5-hydroxy-2-dipropylamino-1,2,3,4-tetrahydronaphthalene, which was more potent than apomorphine but less so than the dihydroxyl analog. The two enantiomers of the monohydroxyl analog were synthesized by conventional methods from an optically active intermediate, 2-benzylamino-5-methoxy-1,2,3,4-tetrahydronaphthalene. The resolution of this amine was performed with the aid of mandelic acid. Dopaminergic activity was found to be confined to the levo enantiomer. Requirements for both substitution and chirality in the tetralines were found to correspond closely to those known for the dopaminergic aporphines.

Synthesis and pharmacology of some 2-aminotetralins. Dopamine receptor agonists.

A series of 2-amino-1,2,3,4-tetrahydronaphthalene compounds bearing substituents on the nitrogen and in the aromatic ring was synthesized from beta-tetralone intermediates. Compounds were screened in vivo for dopaminergic activity using tests in which apomorphine was especially active. It was found that apparent dopaminergic activity is inherent in 2-dialkylaminotetralins, the dipropylamine substitution being the most consistently productive amine group studies. Activity was greatly enhanced by proper substitution in the aromatic ring. The 5,6-dihydroxy group was the best potentiating group found. These data support the idea that the extended conformation for the phenylethylamine moiety of ampmorphine and dopamine is favorable for dopaminergic agonist activity. They also suggest that an unetherified catechol group may not be essential for such activity.